Retinoic acid treatment and cell aggregation independently regulate alternative splicing in P19 cells during neural differentiation
Retinoic acid treatment and cell aggregation independently regulate alternative splicing in P19 cells during neural differentiation
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DOI：
10.1042/cbi20090332
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发表时间：
2010-06-01
影响因子：
3.9
通讯作者：
Tsukahara, Toshifumi
中科院分区：
文献类型：
--
作者：
Alam, A. H. M. Khurshid;Suzuki, Hitoshi;Tsukahara, Toshifumi
为诱导P19细胞的神经分化，需要两种不同的处理方法，即视黄酸（RA）和细胞聚集。然而，尚无报道表明单独使用RA处理或单独进行细胞聚集能够控制P19细胞中的可变剪接调控。因此，我们关注P19细胞中神经诱导（RA处理和/或细胞聚集）产生的可变剪接效应。我们分析了几个基因的剪接模式，包括5 - 羟色胺3A受体（5 - HT3R - A）、α-辅肌动蛋白1（Actn1）、CUG结合蛋白2（CUGBP2）和多聚嘧啶区结合蛋白（PTB），这些基因在P19细胞的早期神经诱导过程中表现出不同的反应。我们在此表明，单独的RA处理改变了5 - HT3R - A的可变剪接机制。单独的细胞聚集控制Actn1的可变剪接调控。两种处理方法（RA和细胞聚集）相互补充并调节CUGBP2的可变剪接机制。然而，PTB与RA和细胞聚集无关。综上所述，我们的结果表明，在神经分化过程中，RA处理和细胞聚集在P19细胞的早期阶段独立地调节可变剪接机制。
To induce neural differentiation of P19 cells, two different treatments, RA (retinoic acid) and cell aggregation, are required. However, there has been no report that RA treatment alone or cell aggregation alone could control alternative splicing regulation in P19 cells. Therefore, we focused on alternative splicing effects by neural induction (RA treatment and/or cell aggregation) in P19 cells. We analysed the splicing patterns of several genes, including 5-HT3R-A (5-hydroxytryptamine receptor), Actn1 (actinin alpha1), CUGBP2 (CUG-binding protein) and PTB (polypyrimidine track-binding protein), which showed different responses during the early neural induction of P19 cells. We show here that RA treatment alone changes the alternative splice mechanism of 5-HT3R-A. Cell aggregation alone controls alternative splicing regulation of Actn1. Both treatments (RA and cell aggregation) compensate and regulate the alternative splicing mechanism of CUGBP2. However, PTB is independent of RA and cell aggregation. Taken together, our results suggest that RA treatment and cell aggregation independently regulate the alternative splicing mechanism in the early stage of P19 cells during neural differentiation.